Abstract
Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.
Original language | English |
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Pages (from-to) | 7824-7831 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 16 |
Issue number | 16 |
DOIs | |
Publication status | Published - Aug 15 2008 |
Externally published | Yes |
Keywords
- Antitumor
- Athymic mice
- Cinnolines
- Cytotoxicity
- Human tumor xenografts
- Isoquino[4,3-c]cinnolin-12-ones
- Multidrug resistance
- Topoisomerase
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science